Bypassing the Blood-Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies.
Bypassing the Blood-Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies.
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DOI：
10.3390/pharmaceutics12121134
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发表时间：
2020-11-24
期刊：
影响因子：
5.4
通讯作者：
Feja M
中科院分区：
文献类型：
--
作者：
Gernert M;Feja M
癫痫是一种常见的慢性神经系统疾病，其特征是反复发作的中枢性无端癫痫。治疗的主要方法是通过系统应用抗癫痫药物(ASD)对癫痫进行症状抑制。癫痫的系统药物治疗面临两个主要挑战。首先，全身药物治疗(通常是终生的)的不良反应很常见，其次，大约三分之一的癫痫患者的癫痫发作对全身药物治疗无效。尤其是癫痫患者的耐药性仍然是一个尚未得到满足的临床需求，尽管最近引入了新的ASD。除了其他假说外，癫痫引起的血脑屏障(BBB)的改变被认为可以阻止ASD进入必要的脑实质，从而参与导致耐药癫痫。尽管这是一种侵入性手术，但通过定向的颅内给药绕过血脑屏障是一种有吸引力的方法，可以绕过血脑屏障相关的耐药机制，降低全身和神经系统不良反应的风险。此外，它还提供了在适当的靶区达到较高的局部药物浓度的可能性，同时将其他大脑或外围区域的药物浓度降至最低，以及使用不适合全身给药的其他有毒药物。在我们的综述中，我们对癫痫的直接颅内给药的实验和临床研究进行了综述。我们还讨论了与癫痫的颅内药物治疗相关的挑战。
Epilepsies are common chronic neurological diseases characterized by recurrent unprovoked seizures of central origin. The mainstay of treatment involves symptomatic suppression of seizures with systemically applied antiseizure drugs (ASDs). Systemic pharmacotherapies for epilepsies are facing two main challenges. First, adverse effects from (often life-long) systemic drug treatment are common, and second, about one-third of patients with epilepsy have seizures refractory to systemic pharmacotherapy. Especially the drug resistance in epilepsies remains an unmet clinical need despite the recent introduction of new ASDs. Apart from other hypotheses, epilepsy-induced alterations of the blood–brain barrier (BBB) are thought to prevent ASDs from entering the brain parenchyma in necessary amounts, thereby being involved in causing drug-resistant epilepsy. Although an invasive procedure, bypassing the BBB by targeted intracranial drug delivery is an attractive approach to circumvent BBB-associated drug resistance mechanisms and to lower the risk of systemic and neurologic adverse effects. Additionally, it offers the possibility of reaching higher local drug concentrations in appropriate target regions while minimizing them in other brain or peripheral areas, as well as using otherwise toxic drugs not suitable for systemic administration. In our review, we give an overview of experimental and clinical studies conducted on direct intracranial drug delivery in epilepsies. We also discuss challenges associated with intracranial pharmacotherapy for epilepsies.
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